A trypsin crystal held in a fibre cryoloop at 100 K for irradiation by an X-ray beam, also showing a 25 micron light beam used to monitor the optical absorption changes during the experiment by means of an on-line UV-vis-microspectrophotometer: an example of the use of simultaneous complementary techniques now possible at most modern synchrotron sources

Professor Elspeth Garman’s invited review in a recent special issue of Science charts the history of X-ray crystallography and looks forward to how challenges may be overcome by current and future developments (1).

In a field that has attracted 28 Nobel Prizes, starting in 1915 with the Bragg father-and-son team, there are plenty of milestones – from the initial observation of diffraction from pepsin crystals, to the recent characterisation of the entire ribosome (around 280,000 nonhydrogen atoms) and of G-protein coupled receptors in different conformational states.

Synchrotron facilities are now equipped with a range of valuable features. Many offer sample-mounting robots, microfocus beams, and the ability to collect simultaneous supplementary (e.g. spectroscopic) data. Although it is still not yet possible to predict the conditions under which a particular protein will crystallise, crystallisation robots remove much of the drudgery from the search for suitable conditions.

The review discusses promising new developments in macromolecular crystallography that are likely to push the field on further. The 30% of proteins coded by the human genome which are membrane proteins presents a particular challenge for conventional techniques. This has spurred the development of new approaches, for growing crystals and for screening putative crystals for their suitability.

Other growth areas include room-temperature structure determination at synchrotrons, and the possibilities offered by x-ray free-electron lasers which could potentially enable the imaging of single molecules.